Method for Inhibiting HIV Replication in Mammal and Human Cells

Abstract

The present invention describes a method to inhibit replication of the human immunodeficiency virus (HIV) by negatively modulating or altering the cytoskeleton, more precisely the proteins forming the intermediate cytoskeletal filaments, wherein the said proteins are vimentin and/or keratin-10. The replication of the virus is inhibited in human cells by intervening in the structure of these proteins. The present invention is also related to the use of agents, which comprise peptides and/or interfering RNA and/or lipidic compounds, said agents producing a negative modulation or alteration of the cytoskeleton to prevent or to treat the HIV infection. The invention provides means and methods for altering the cytoskeleton/filament structure of cells, as a result of which the infection of human cells by HIV is disturbed and can even be completely inhibited. The cytoskeleton is altered by reducing the amount of vimentin and/or keratin (e.g. by transcriptional control using interfering RNA) or by using peptides that disrupt the cytoskeleton.

Description

TECHNICAL FIELD[0001]The present invention is related to the field of biomedicine, and more precisely to therapies against infections, and particularly against the infection of the human immunodeficiency virus (HIV). The present invention describes a method to inhibit HIV replication by altering the cytoskeleton, specifically those proteins forming the cytoskeletal intermediate filaments (IFs). The present invention also relates to the use of agents which negatively modulate or modify the cytoskeleton for the purpose of manufacturing drugs to prevent and to treat HIV infection.BACKGROUND OF THE INVENTION[0002]The emergence of the HIV / acquired immunodeficiency syndrome pandemic is among the most significant health problems arising worldwide in the last thirty years.[0003]It has led to the development of antiretroviral treatments able to stop the progression of infection and reducing mortality (De Cock K, Crowley S P, Lo Y R, Granich R M, Williams B G. Boletin de la Organizacióon Mund...

AI Technical Summary

Benefits of technology

[0115]The present invention is advantageous over the currently available antiretroviral drugs because it avoids viral resistance or reduces its probabilities for occurrence to the minimum. This is based on the cellular endogenous rather than viral origin of IFs and in particular vimentin and keratin-10 proteins.

[0116]The drugs of the present invention act with a high inhibition capacity through mechanisms different to those already described in the prior art. Therefore, its combination with currently available therapeutic drugs specific for the HIV infection could enhance the effectiveness of anti-HIV treatments.

[0117]On the other hand, the use of the therapeutic agents of the present invention could be combined with novel therapeutic alternatives proposed in the state of the art, such as transplantation of stem cells bearing endogenous modified genes.

[0118]The present invention offers a new therapy to patients resistant to multiple drugs, which represent a high percent among patients treated with the currently available therapy.

[0119]Once formulated, the pharmaceutical compositions of the invention can be (1) administered directly to the subject; (2) delivered ex vivo, to cells derived from the subject; or (3) delivered in vitro for expression of recombinant proteins.

[0120]Direct delivery of the compositions will generally be accomplished by injection, either subcutaneously, intraperitoneally, intravenously or intramuscularly, or delivered to the interstitial space of a tissue. The compositions can also be administered into the nervous system. Other modes of administration include topical, oral, suppositories, and transdermal applications, needles, and particle guns or hyposprays. Dosage treatment may be a single dose schedule or a multiple dose schedule.

Problems solved by technology

The appearance of HIV variants that are resistant against the currently available anti-HIV drugs and the poor adherence to treatment by patients remain as the main causes for therapeutic failure.

Nevertheless, the multi-drug therapy does not eliminate HIV completely, with long-term treatment generally resulting in resistance to several drugs.

Half of the patients receiving combined anti-HIV therapy do not completely respond to treatment, mainly due to viral resistance to one or more of the drugs applied.

Additionally, viral resistance has been detected in recently infected patients, significantly limiting the therapeutic options for those patients.

The adherence to HIV antiretroviral therapy is one of the most debatable issues regarding HAART, and specifically PR (protease) inhibitors, due to the fast appearance of viral resistance if the drugs are irregularly taken or the treatment is interrupted.

Combination therapy delays progression to AIDS, but does not cure the infected patients (Marsden M D, Zack J A 2009.

Even when therapy has transformed this infection into a chronic disease rather than a fatal disease and also increased the life expectancy among patients to levels similar to those of the general population, it still represents unsolved serious problems which require the search for new strategies to decrease the used of antiretrovirals.

All the disadvantages of the available anti-HIV therapies support the need for new anti-HIV drugs differing mostly on their mechanisms and / or targets of action.

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